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This study investigated intraocular pressure (IOP) in Dutch belted rabbits using two different tonometers, rebound tonometry (TonoVet Plus; TVP) and a Tonopen (Tono-Pen AVIA Vet; TPA). Post-pubescent male Dutch belted rabbits aged 36 weeks (n = 10 animals) were used in the study. IOP measurements were conducted every 2 weeks for 22 weeks using TVP and TPA on both eyes of each rabbit. The average IOP measurements were compared by the paired Student’s t-test. Pairwise Pearson’s correlation coefficients and Bland–Altman statistics were used. The overall mean IOP measured with TPA was significantly higher than that with TVP (23.5 ± 4.9 vs. 21.8 ± 2.4 mmHg for the right eyes; P = 0.045, and 23.0 ± 4.7 vs. 21.5 ± 2.4 mmHg for the left eyes; P = 0.047). Both tonometers tended to show increased IOP readings with age, and positive correlations between IOP and age were observed with both TPA (r = 0.95, P < 0.001 for right eyes; r = 0.95, P < 0.001 for left eyes) and TVP (r = 0.91, P < 0.001 for right eyes; r = 0.64, P = 0.024 for left eyes). The average bias calculated by subtracting TPA from TVP was − 1.60 (95% confidence intervals − 1.927, − 1.281) mmHg. IOP in post-pubescent Dutch belted rabbits tended to increase with age throughout the 22 week study. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) stands as the most prevalent neurodegenerative disorder, characterized by a multitude of pathological manifestations, prominently marked by the aggregation of amyloid beta. Recent investigations have revealed a compelling association between excessive adiposity and glial activation, further correlating with cognitive impairments. Additionally, alterations in levels of insulin-like growth factor 1 (IGF-1) have been reported in individuals with metabolic conditions accompanied by memory dysfunction. Hence, our research endeavors to comprehensively explore the impact of IGF-1 on the hippocampus and adipose tissue in the context of Alzheimer's disease. To address this, we have conducted an in-depth analysis utilizing APP/PS2 transgenic mice, recognized as a well-established mouse model for Alzheimer's disease. Upon administering IGF-1 injections to the APP/PS2 mice, we observed notable alterations in their behavioral patterns, prompting us to undertake a comprehensive transcriptomic analysis of both the hippocampal and adipose tissues. Our data unveiled significant modifications in the functional profiles of these tissues. Specifically, in the hippocampus, we identified changes associated with synaptic activity and neuroinflammation. Concurrently, the adipose tissue displayed shifts in processes related to fat browning and cell death signaling. In addition to these findings, our analysis enabled the identification of a collection of long non-coding RNAs and circular RNAs that exhibited significant changes in expression subsequent to the administration of IGF-1 injections. Furthermore, we endeavored to predict the potential roles of these identified RNA molecules within the context of our study. In summary, our study offers valuable transcriptome data for hippocampal and adipose tissues within an Alzheimer's disease model and posits a significant role for IGF-1 within both the hippocampus and adipose tissue. [ABSTRACT FROM AUTHOR]

The placebo effect and its potential determinants in ocular hypotensive therapy. The placebo effect has been studied and documented within a wide clinical context. It remains unclear whether placebo is effective in glaucoma treatment or, if so, which factors are determinative of effect size (ES). Randomized controlled trials (RCTs) of topical ocular hypotensive therapy for patients with open-angle glaucoma or ocular hypertension, conducted through June 2, 2022, were included. First, a perceived placebo effect was measured as the overall intraocular pressure (IOP) change from the baseline. It was evaluated in terms of the ES (mean difference between the baseline and the end point) and then was compared with the ES, as obtained from the untreated control participant to obtain a true placebo effect. The primary outcome was ES based on 4 weeks of treatment. Meta-analysis–based statistical pooling was performed where appropriate, and 95% confidence intervals (CIs) were used for comparison. Potential placebo effect determinants were scrutinized using a multiple meta-regression model (PROSPERO identifier, CRD42022348098). A total of 40 RCTs (7829 eyes) with 33 placebo groups (2055 eyes) along with 7 untreated groups (1184 eyes) were included. Among placebo-controlled trials, placebo was determined to be effective in lowering IOP (ES, −1.30 mmHg; 95% CI, −1.75 to −0.84 mmHg). Using NMA, the ES for placebo was −2.27 mmHg (95% CI, −3.52 to −1.01 mmHg) greater than ES for untreated control participants.. According to the multiple meta-regression model, the active treatment ES was a significant factor to predict the amount of placebo effect. Placebo additionally lowered IOP by −0.45 mmHg per −1 mmHg of active treatment effect. Add-on study design and larger sample size also were associated with greater amount of placebo effect. No publication bias was evident in either a funnel plot or the Begg and Mazumdar adjusted rank correlation test results (P = 0.24). This meta-analysis indicated that placebo is effective in lowering IOP and is superior to the effect observed for the untreated control participants. However, caution is required in interpreting the results because of the small number of untreated controlled trials and potential bias from the lack of direct comparison between the placebo and untreated arms. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a chronic metabolic disease accompanied by neuropathological and neuropsychiatric features, including memory deficits, psychomotor dysfunction, depression, and anxiety. Alzheimer's disease (AD), the most common neurodegenerative disease, is characterized by tau hyperphosphorylation, excessive amyloid beta (Aβ) accumulation, the formation of fibrillary tangles, hippocampus atrophy, and neuroinflammation. Recent studies have suggested a positive correlation between HE and AD. Some studies reported that an impaired cholesterol pathway, abnormal bile acid secretion, excessive ammonia level, impaired Aβ clearance, astrocytic dysfunction, and abnormal γ-aminobutyric acid GABAergic neuronal signaling in HE may also be involved in AD pathology. However, the mechanisms and related genes involved in AD-like pathology in the HE brain are unclear. Thus, we compared the cortical transcriptome profile between an HE mouse model, bile duct ligation (BDL), and an AD mouse model, the 5×FAD. Our study showed that the expression of many genes implicated in HE is associated with neuronal dysfunction in AD mice. We found changes in various protein-coding RNAs, implicated in synapses, neurogenesis, neuron projection, neuron differentiation, and neurite outgrowth, and non-coding RNAs possibly associated with neuropathology. Our data provide an important resource for further studies to elucidate AD-like pathophysiology in HE patients. [ABSTRACT FROM AUTHOR]

Background: Diabetes causes the dysregulation of several organs, and these effects are often closely associated with changes in the expression of long non-coding RNAs (lncRNAs), a group of non-coding RNAs, within these tissues. Previous studies have described a variety of changes in the expression profile of several lncRNAs from different organs in response to the pathogenesis of diabetes. However, none of these studies compared the expression profiles of these lncRNAs between these organs. This study was designed to identify common and specific lncRNAs involved in the progression of diabetes in the skeletal muscles and kidneys. Methods: Publicly available RNA sequencing data of diabetic patients was obtained from the Gene Expression Omnibus database. By analyzing the expression of lncRNAs in these datasets, differentially expressed lncRNAs in each tissue between non-diabetic and diabetic patients were identified. To identify any lncRNAs changed in common in both kidney and muscle tissues, those lncRNAs that are significantly dysregulated in both datasets were selected. Results: These evaluations identified a series of novel lncRNAs unique to each organ and several transcripts that were common to both skeletal muscle and kidney tissues in these patients. Interestingly, the genomic location of these lncRNAs suggests that they reside in close proximity to several protein-coding genes known to be related to diabetes suggesting that these lncRNAs may have a regulatory relationship with their neighboring genes. Conclusion: These results offer valuable insights into the role of lncRNAs during the pathogenesis of diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate ocular hypotensive efficacy and the safety of sovesudil (formally known as PHP‐201), a novel Rho‐associated protein kinase (ROCK) inhibitor, in patients with normal‐tension glaucoma (NTG). Design: Multicentre, prospective, double‐masked, randomized, placebo‐controlled, parallel clinical study. Methods: Patients with NTG (unmedicated baseline IOP ≤ 21 mmHg) were randomized in 3 groups and treated with sovesudil in concentrations of 0.25% and 0.5%, or with a placebo three times daily (TID) for 4 weeks. The primary end‐point was the mean diurnal IOP change from the baseline at week 4. Safety was recorded over a 4‐week treatment period and the following 2‐week observation period. Results: A total of 119 patients were included in the primary efficacy analysis. The mean diurnal IOP change from the baseline at week 4 was −1.56 mmHg for the high‐dose group, −1.10 mmHg for the low‐dose group and −0.65 mmHg for the placebo group. The difference between the high‐dose and the placebo groups was −0.91 mmHg (95% confidence intervals: −1.73, −0.09). 0.5% sovesudil TID met the criteria for superiority to the placebo. The most frequent ocular adverse event among sovesudil‐treated patients was conjunctival hyperaemia (24.4% for the high‐dose and 17.5% for the low‐dose group) and predominately classified as mild. Conclusions: Sovesudil 0.25% and 0.5% TID showed statistically significant IOP‐lowering effects and 0.5% concentration's IOP‐lowering effects met the superiority criteria in comparison with the placebo at week 4. Sovesudil was well tolerated with mild adverse events including relatively low incidence of conjunctival hyperaemia in patients with NTG. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate longitudinal changes of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) profile arising in the course of childhood myopia progression. Thirty-six eyes of 36 healthy children who showed myopia progression (spherical equivalent [SE] decrease of ≥ 2.0 diopters [D]) were included. To account for the axial-elongation-induced magnification effect on spectral-domain optical coherence tomography (SD-OCT) measurements, we calculated the proportion of quadrant-cpRNFLT distribution (i.e., the percentage of cpRNFLT within a single quadrant of total cpRNFLT). During 4.1 ± 1.1 years, the mean SE changed from -1.3 ± 0.9 to -4.3 ± 0.8D, and both the optic disc tilt ratio and the torsional angle increased (both P < 0.001). In the temporal quadrant, the cpRNFLT proportion was increased from 19.2 ± 1.86 to 24.4 ± 2.30% (P < 0.001). The cpRNFLT proportion in 3 quadrants (i.e., superior, inferior, nasal) showed decreases (all P < 0.001). Between baseline and follow up, the scan-circle location as determined by OCT was shifted mostly (94%; 34 of 36 eyes) toward the nasal side of the optic disc. With scan-circle repositioning to match the baseline, cpRNFLT distribution proportions did not show any significant difference between the baseline and follow up (all P > 0.05). For longitudinal evaluations of patients with myopia progression, scan-circle alteration should be given due consideration. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the long-term visual outcomes in children with primary congenital glaucoma and determined the factors associated with the final visual outcomes. Methods: Medical records of children with primary congenital glaucoma between 2005 and 2016, seen at Seoul National University Children's Hospital in South Korea, were reviewed. The minimum follow-up period after surgery for primary congenital glaucoma was 3 years. Visual acuity (VA) was categorized into good (≧20/70) and poor (< 20/70). Factors including age, VA, refractive errors, intraocular pressure (IOP), laterality, and cup-to-disc (C/D) ratio were compared between the groups. Results: A total of 71 eyes of 44 patients were included. The patients' age at the time of surgery was 14.7 ± 12.2 months. The mean IOP was 28.3 ± 7.0 mmHg. During 6.7 ± 2.7 years of mean follow-up after surgery, 39 eyes (54.9%) needed occlusion treatment. After occlusion, patients with lower IOP values, lesser additional surgeries, reversal of optic disc cupping, and better initially measured VA achieved a better visual outcome. At the final assessment, the mean age was 7.8 ± 2.6 years, and the mean VA gain was 15.0 ± 19.4 letters. There were 44 eyes (62.0%) with VA ≧20/70. Conclusions: In children with primary congenital glaucoma, IOP control and the optic disc configuration over time are important factors associated with visual outcome. Regular follow-up and correction of refractive errors—along with occlusion for those with difference in VA between the two eyes—might be helpful for achieving better visual outcomes. [ABSTRACT FROM AUTHOR]

Depressive disorder is one of the most widespread forms of psychiatric pathology, worldwide. According to a report by the World Health Organization, the number of people with depression, globally, is increasing dramatically with each year. Previous studies have demonstrated that various factors, including genetics and environmental stress, contribute to the risk of depression. As such, it is crucial to develop a detailed understanding of the pathogenesis of depressive disorder and animal studies are essential for identifying the mechanisms and genetic disorders underlying depression. Recently, many researchers have reported on the pathology of depression via various models of depressive disorder. Given that different animal models of depression show differences in terms of patterns of depressive behavior and pathology, the comparison between depressive animal models is necessary for progress in the field of the depression study. However, the various animal models of depression have not been fully compared or evaluated until now. In this paper, we reviewed the pathophysiology of the depressive disorder and its current animal models with the analysis of their transcriptomic profiles. We provide insights for selecting different animal models for the study of depression. [ABSTRACT FROM AUTHOR]

Aims/Purpose: To assess the comparative efficacies of surgical interventions for childhood glaucoma (CG). Methods: Through electronic database searches up to August 7, 2022, randomized controlled trials (RCTs) involving surgical interventions for CG were identified. A meta‐analysis was conducted to compare the surgical interventions: Conventional partial trabeculotomy ([CPT] control), 240‐degree trabeculotomy, Illuminated microcatheter‐assisted circumferential trabeculotomy (IMCT), Viscocanalostomy, Visco‐circumferential‐suture‐trabeculotomy, Goniotomy, Laser goniotomy, Kahook dual blade ab‐interno trabeculectomy, Trabeculectomy with mitomycin C, Trabeculectomy with modified scleral bed, Deep sclerectomy, Combined trabeculectomy‐trabeculotomy with mitomycin C, and Baerveldt implant. The main outcome measures were postoperative 6‐month mean intraocular pressure (IOP) reduction and surgical success rate. The mean differences (MDs) or odds ratios (ORs) were obtained using a random‐effects model, and the efficacies were ranked by P‐score. Results: Sixteen (16) RCTs were eligible for inclusion in the analysis, involving 710 eyes of 485 participants and 13 surgical interventions, which formed a 14‐node network. IMCT was superior to CPT in both IOP reduction (MD [95% CI], −3.10 [−5.50 to −0.69]) and surgical success rate (OR [95% CI], 4.38 [1.61 to 11.96]), while the MD and OR comparing the other surgical interventions with CPT were not statistically significant. Moreover, the IMCT was ranked as the most efficacious surgical intervention for success rate (P‐score = 0.777). Conclusions: This meta‐analysis revealed that IMCT is more effective than CPT and might be the most efficacious surgical intervention for CG. [ABSTRACT FROM AUTHOR]

• RNA sequencing datasets were analyzed to identify common lncRNAs differentially expressed after macrophage induction. • Commonly altered lncRNAs were established in human and mouse macrophages induction. • The lncRNAs list will help elucidate the regulatory pathways underlying macrophage activation and phenotypic fate. Macrophages are the primary cell type in the immune system and are activated in response to diverse external stimuli. They can exert inflammatory or anti-inflammatory responses depending on the type of stimuli in the system, and as such rely on a complex network of diverse signaling pathways to function. Non-coding RNAs have recently been established as an important class of regulators linked to the activation of macrophages. Although the roles of many microRNAs have been described, the majority of the other types of regulatory non-coding RNAs, including long non-coding RNAs (lncRNAs), remain undefined. In this study, we performed a comprehensive analysis of several large RNA sequencing datasets to identify common lncRNAs differentially expressed after M1 or M2 macrophage induction. We identified the lncRNAs that underwent significant changes in each dataset and established a list of commonly altered lncRNAs. We expect that our data will act as a valuable resource for future studies designed to uncover the roles of these lncRNAs in determining macrophage fates. [ABSTRACT FROM AUTHOR]

We developed a hybrid deep learning model (HDLM) algorithm that quantitatively predicts macular ganglion cell-inner plexiform layer (mGCIPL) thickness from red-free retinal nerve fiber layer photographs (RNFLPs). A total of 789 pairs of RNFLPs and spectral domain-optical coherence tomography (SD-OCT) scans for 431 eyes of 259 participants (183 eyes of 114 healthy controls, 68 eyes of 46 glaucoma suspects, and 180 eyes of 99 glaucoma patients) were enrolled. An HDLM was built by combining a pre-trained deep learning network and support vector machine. The correlation coefficient and mean absolute error (MAE) between the predicted and measured mGCIPL thicknesses were calculated. The measured (OCT-based) and predicted (HDLM-based) average mGCIPL thicknesses were 73.96 ± 8.81 µm and 73.92 ± 7.36 µm, respectively (P = 0.844). The predicted mGCIPL thickness showed a strong correlation and good agreement with the measured mGCIPL thickness (Correlation coefficient r = 0.739; P < 0.001; MAE = 4.76 µm). Even when the peripapillary area (diameter: 1.5 disc diameters) was masked, the correlation (r = 0.713; P < 0.001) and agreement (MAE = 4.87 µm) were not changed significantly (P = 0.378 and 0.724, respectively). The trained HDLM algorithm showed a great capability for mGCIPL thickness prediction from RNFLPs. [ABSTRACT FROM AUTHOR]

Purpose: To assess the performance of machine learning classifiers for prediction of progression of normal-tension glaucoma (NTG) in young myopic patients. Study design: Cross-sectional study. Methods: One hundred and fifty-five eyes of 155 myopic NTG patients (axial length [AL] ≥ 24.00 mm and refractive error ≤ − 3.0 D) between the ages of 20 and 40 were enrolled and divided into training (110) and test (45) sets. Sixty-five eyes showed glaucoma progression as defined by standard automated perimetry, while 91 eyes (nonprogressors) had been stable over the course of a follow-up period of at least 3 years. Two machine learning classifiers were built using the random forest and extremely randomized trees (extra-trees) models. Baseline clinical measurements obtained only at the initial visit were used as input features. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the accuracy of prediction. Results: Mean age and AL did not significantly differ between the 2 groups on either the training or the test set. The extra-trees model achieved an AUC of 0.881 [95% CI 0.814–0.945], higher than that of the random forest model (0.811 [0.731–0.888]; P = 0.010). The extra-trees model also outperformed all the clinical measurements for prediction of NTG progression, including average macular ganglion cell-inner plexiform layer thickness (0.735 [0.639–0.831]) and average circumpapillary retinal nerve fiber layer thickness (0.691 [0.590–0.792]; both P < 0.001). Conclusions: In young myopic patients, the machine learning classifier with the extra-trees model can predict glaucomatous progression more effectively than clinical diagnostic parameters. [ABSTRACT FROM AUTHOR]

This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P < 0.001). The smaller/larger HF N95 amplitude ratio of the PPG group was found to be smaller than that of the control group (0.73 ± 0.20 vs. 0.86 ± 0.12; P = 0.003) and showed positive correlations with affected HF average ganglion cell-inner plexiform layer (GCIPL) thickness (r = 0.377, P = 0.034) and with average GCIPL thickness (r = 0.341, P = 0.005). The smaller/larger HF N95 amplitude ratio did not significantly change with age (β = − 0.005, P = 0.195), whereas the full-field N95 amplitude showed a negative correlation with age (β = − 0.081, P < 0.001). HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To investigate, in primary open-angle glaucoma (POAG) and healthy subjects, the pattern and magnitude of diurnal variation in optical coherence tomography angiography (OCTA) retinal vessel density (RVD). Design: Prospective, observational cross-sectional study. Participants: A prospective study was conducted on 20POAG patients and 19 healthy subjects. Methods: Peripapillary/macular RVD (using swept-source OCTA), intraocular pressure (IOP), and systemic blood pressure (BP) were measured five times a day (8 a.m., 11 a.m., 2 p.m.,5 p.m. and 8 p.m.). The magnitudes and patterns of diurnal changes in RVD, diastolic BP, and mean ocular-perfusion pressure (MOPP) were analyzed and compared between the POAG patients and the healthy subjects. Main outcome measures: The patterns and magnitudes of diurnal RVD change in OCTA. Results: Intra-visit repeatability (0.755–0.943) and inter-visit reproducibility (0.843–0.986) for the RVD measurements showed excellent reliability. In the POAG patients, the magnitude of diurnal change in peripapillary RVD (9.71±7.04%) and macular RVD (7.22±4.73%) were significantly greater than that in the healthy group (5.73±3.85%, P = 0.013 and 5.51±3.45%, P = 0.042, respectively). The magnitudes of diurnal variations of IOP and MOPP in the POAG group likewise were greater than those in the healthy group (P = 0.003 and 0.039). As for the patterns of diurnal RVD change, interestingly, at 8 p.m., the macular RVD of the healthy group increased to the highest level (44.12±2.95%) while that of the POAG group decreased to the lowest level (40.41±2.54%). Conclusions: In POAG eyes, diurnal change of IOP, MOPP and RVD was significantly greater than in the healthy eyes. These findings suggest that diurnal RVD changes might reflect the hemodynamic variation of POAG. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of reading or writing on a smartphone in terms of intraocular pressure (IOP) changes. Design: Prospective, comparative case series. Participants: Thirty-nine (39) healthy young (age < 40) volunteers. Methods: The participants were requested to conduct standardized work (i.e., read a sample text on single mobile device and subsequently type it on the same device) under daylight [300 lux] and low-light [100 lux] conditions independently on consecutive days. On each day, three sets of IOP measurements (total: 7) using a rebound tonometer (iCare PRO; Tiolat, Helsinki, Finland) were performed: (1) pre-work (baseline) [2 measurements], (2) during smartphone work [5, 15, and 25 minutes], and (3) post-work [5 and 15 minutes]. Main outcome measures: Changes in IOP at different check-out points. Results: Under the daylight condition, the mean baseline IOP was 13.7 ± 1.8 mmHg, and the mean IOP increased after 5 minutes of work (14.1 ± 1.8 mmHg; +2.0 ± 1.9%; P < 0.001). When the smartphone work lasted for 15 minutes, the IOP showed a further significant increase (15.5 ± 1.7 mmHg; +12.9 ± 4.4%; P < 0.001), which persisted over the course of the 25 minutes of smartphone work (15.3 ± 1.8 mmHg; +11.1 ± 3.9%; P < 0.001); then, after stopping work for 5 minutes, the IOP was restored (13.9 ± 1.7 mmHg; +0.9 ± 2.1%; P = 0.220). Under the low-light condition, the mean IOP was significantly increased immediately after 5 minutes of smartphone work (from 13.9 ± 1.9 to 15.6 ± 1.8 mmHg; +12.1 ± 4.8%; P < 0.001); this IOP increase continued: 17.3 ± 1.9 [+24.7 ± 10.3%] at 15 minutes’ work, and 17.0 ± 1.7 mmHg [+23.1 ± 9.5%] at 25 minutes’ work (P < 0.001 at both check-out points). Five minutes after stopping the smartphone work, interestingly, the IOP significantly dropped, to a level even lower than that of the pre-work (12.8 ± 1.9 mmHg; -8.1 ± 3.0%; P < 0.001), and at post-work 15 minutes, the IOP returned to the baseline (13.9 ± 1.8 mmHg; -0.3 ± 2.6%; P = 0.360). Conclusions: In healthy young subjects, reading or writing on smartphone significantly increased IOP, and the changes of IOP were faster and greater under the low-light condition. Smartphone users who are concerned about IOP fluctuation are advised to (1) take a break if they read or write on smartphone for more than 5 minutes, and (2) avoid using smartphones wherever possible in dark places. [ABSTRACT FROM AUTHOR]

Little is known about the diagnostic utility of three-dimensional neuroretinal rim thickness (3D-NRRT) for differentiating patients with superior segmental optic nerve hypoplasia (SSOH) from normal-tension glaucoma (NTG). Since SSOH is defined by characteristic optic nerve head features, investigation of diagnostic usefulness of 3D-NRRT is necessary. In this cross-sectional study, 49 SSOH eyes, 52 NTG eyes, and 41 normal eyes were enrolled. Retinal nerve fiber layer thickness (RNFLT) and 3D-NRRT values, as obtained in the right-eye orientation by optical coherence tomography (OCT), were recorded. On RNFLT clock-hour comparison, the 11–3 clock-hour sectors were significantly thinner for SSOH than for NTG (all P < 0.01). As for 3D-NRRT, whereas the 1 and 2 sectors were significantly thinner for SSOH (P < 0.001, P = 0.004), the 6–11 sectors were significantly thinner for NTG (all P < 0.01). The area under receiver operating characteristic (AUROC) curves of the superior and nasal quadrants of RNFLT (0.838, 0.729) were significantly greater than those of 3D-NRRT (0.518, 0.588; P < 0.001, P = 0.043). However, the AUROCs of the inferior and temporal quadrants were significantly greater for 3D-NRRT (0.728, 0.760) than for RNFLT (0.527, 0.550; P = 0.008, P = 0.019). The appropriate use of 3D-NRRT can be useful in differentiating SSOH from NTG. [ABSTRACT FROM AUTHOR]

We investigated the internal morphology of filtration blebs after XEN gel stent implantation using anterior segment optical coherence tomography (AS-OCT) and identified factors related to intraocular pressure (IOP) postoperatively. Eighteen eyes of 18 patients who had undergone XEN gel stent implantation were analyzed. Blebs were imaged using Visante OCT (Carl Zeiss Meditec AG, Germany) at 6 months and 1 year after surgery and evaluated for quantitative parameters including bleb height, maximum height of internal cavity, maximum bleb wall thickness, and maximum bleb epithelial thickness. Subjects were classified into two groups according to the presence or absence of a definite internal cavity between the conjunctiva and sclera using AS-OCT imaging. Nine eyes (50%) were assigned to the internal cavity group and 9 (50%) to the uniform group. Postoperative IOP was significantly lower in the internal cavity group than in the uniform group both at 6 months and 1 year after surgery (p = 0.024 and p = 0.040). Postoperative IOP showed statistically significant negative correlations with bleb height and the height of the internal cavity (Spearman correlation coefficient r = −0.518, p = 0.028 and r = −0.453, p = 0.034, respectively). AS-OCT facilitates analysis of bleb morphology after XEN gel stent implantation. A larger height of the internal cavity of the bleb appeared to correlate with lower IOP after XEN implantation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate optic disc hemorrhage (DH)’s clinical implications to subsequent progression of primary open-angle glaucoma (POAG) in cases of mild-to-moderate myopia. Design: Retrospective comparative study. Participants: (1) Fifty-nine (59) myopic (26.5 mm > axial length [AXL] ≥ 24.0 mm) POAG patients with DH and (2) 59 age-, AXL-, and mean deviation (MD) of visual field (VF)-matched controls without DH were evaluated over the course of a minimum 3.5 years of follow up. For clear assessment of the effect of DH on progression of glaucoma, the patients selected for inclusion in the study were those with stable IOP (i.e., those showing an at least 20% reduction relative to the baseline IOP) whose IOP-lowering medication was not increased, supplemented or changed during the follow-up period. Methods: The patients’ optic disc/retinal nerve fiber layer (RNFL) photographs were independently evaluated by three glaucoma specialists for structural progression of glaucoma. Event-based analysis with Guided Progression Analysis (GPA) software was used to determine their functional progression. The durations of structural and functional progression were compared by Kaplan-Meier life survival analyses. Main outcome measures: Optic disc/RNFL progression and VF progression. Results: The mean follow-up periods between the DH and non-DH groups were not significantly different: in the DH group, 5.6±2.7 years; in the non-DH group, 5.4±2.6 years (P = 0.588). In the DH group, 30 (50.8%) of 59 eyes manifested optic disc/RNFL deterioration; in the non-DH group, however, only 17 (28.8%) of 59 eyes showed structural progression. For the DH group, the cumulative probability of structural glaucoma progression was significantly greater than for the non-DH group (P = 0.001; log rank test). Interestingly, the two groups did not significantly differ in the cumulative probability of functional progression (P = 0.79; log rank test): in the DH group, VF progression was observed in 14 eyes (23.7%); in the non-DH group, in 12 eyes (20.3%). Conclusions: DH was associated with a greater probability of structural progression in medically well-controlled-IOP POAG eyes with mild-to-moderate myopia. However, the relevance of DH to VF progression was not clear over the course of the average 5.5-year duration of the study. [ABSTRACT FROM AUTHOR]

Plutella xylostella and Mythimna separata are destructive insect pests causing damages to agricultural products. In this study, a larvicidal compound was identified by bioassay-guided isolation of methanol extracts of Alpinia katsumadai Hayata, a plant belonging to the Zingiberaceae, against P. xylostella and M. separata larvae. Because many insects, including P. xylostella and M. separate larvae, cannot synthesize sterols, they use phytosterols by converting them to the sterols necessary for hormonopoiesis, and resulting normal development, growth and reproduction. Results of our oil droplet formation test showed that compound 1 inhibited foam cell formation in ox-LDL treated THP-1 cells, suggesting that this compound may be inhibiting the sterol transport in insects. The compound 1 with larvicidal activity was elucidated by spectroscopic analysis ( 1 H NMR, 13 C NMR, and ESI–MS) as 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18- tetracosatetraene. The 50% lethal concentration (LC 50 ) values of compound 1 were 2 μg/mL and 16.9 μg/mL, respectively, against P. xylostella and M. separata larvae. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the rate of thinning in ganglion cell–inner plexiform layer (GCIPL) thickness by optical coherence tomography (OCT) in glaucomatous eyes and to use a trend-based approach to determine its diagnostic ability for detecting glaucoma progression. Design Prospective, observational study. Participants Sixty-five patients with primary open-angle glaucoma with a minimum 3-year follow-up involving serial spectral-domain OCT measurement of GCIPL thickness. Methods Patients were divided into a nonprogressor group (n = 38) and a progressor group (n = 27) on the basis of serial red-free photography or visual field tests. The rates of GCIPL thinning in the global region, affected hemifield, and 6 macular sectors, and the minimum thickness, were determined by linear regression and compared between groups. The area under the receiver operating characteristic curves (AUCs) were calculated for each parameter. The GCIPL thinning rates were compared between affected hemifields and unaffected hemifields. Main Outcome Measures The macular GCIPL thinning rates in the progressor and nonprogressor groups and the ability of the GCIPL thinning rate to diagnose glaucoma progression. Results The GCIPL thinning rate was significantly faster in progressors than in nonprogressors in the global area ( P < 0.001); in the affected hemifield ( P = 0.001); in the temporal, vertical, and nasal sectors of the affected hemifield ( P = 0.017, 0.032, and 0.030, respectively); and in the minimum GCIPL thickness ( P < 0.001). In the temporal sectors, the GCIPL thinning rates were significantly faster in the affected than in the unaffected hemifield ( P = 0.013). The best GCIPL parameters were the global (AUC = 0.791), minimum (AUC = 0.755), inferior hemifield (AUC = 0.708), and affected hemifield (AUC = 0.702) thinning rates. The global circumpapillary retinal nerve fiber layer thinning rate correlated significantly with the global and inferotemporal sector GCIPL thinning rates (rho = 0.259 and 0.366, respectively). Conclusions The GCIPL thinning rate on OCT was significantly faster for patients with glaucoma with progression than for those without progression. The GCIPL thinning rate of the temporal sector was faster in the affected than in the unaffected hemifield, suggesting that the glaucomatous damage may progress locally in a specific sequence. Trend-based analysis of GCIPL thickness on OCT may be useful for assessing glaucoma progression objectively and quantitatively. [ABSTRACT FROM AUTHOR]

Purpose To investigate the temporal relationship between inferior macular ganglion cell–inner plexiform layer (mGCIPL) loss and corresponding peripapillary retinal nerve fiber layer (pRNFL) defect on the optical coherence tomography (OCT) deviation map in glaucoma. Design Retrospective, observational study. Participants A total of 151 patients with early-stage glaucoma (visual field [VF] mean deviation between −1.5 and −5.5 decibels [dB]). Methods Spectral-domain OCT mGCIPL and pRNFL deviation maps were obtained for the baseline (from January 2012 to August 2012) and again for the follow-up (from January 2015 to August 2015). An integrated deviation map thereafter was merged by vascular landmark–guided superimposition of mGCIPL and pRNFL deviation maps onto RNFL imagery. On the basis of an earlier schematic model, the inferotemporal peripapillary area was divided into (1) the macular vulnerability zone (MVZ) and (2) the inferoinferior portion. Main Outcome Measures Temporal sequence of inferior mGCIPL loss and corresponding pRNFL (i.e., pRNFL in MVZ) defect on integrated deviation map. Results At baseline, 99 (65.6%) of the 151 eyes showed inferior mGCIPL loss. In addition, 112 eyes (74.2%) and 5 eyes (3.3%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. At the 3-year follow-up, 112 (74.2%) of the eyes showed inferior mGCIPL loss, whereas 123 eyes (81.5%) and 25 eyes (16.6%) showed inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. Ninety-four eyes initially showed inferior mGCIPL loss without pRNFL defect in the MVZ; among them, 19 (20.2%) subsequently showed defect during the 3-year follow-up interval. Meanwhile, among the 52 eyes without preexisting inferior mGCIPL loss, only 1 (1.9%; P < 0.001) developed a pRNFL defect in the MVZ during the 3-year follow-up interval. Conclusions In eyes with early glaucoma, mGCIPL change is frequently detected before corresponding pRNFL change. This could be the result of a superior sensitivity of mGCIPL deviation map that allows detection of an abnormality in the mGCIPL thickness earlier. In this light, OCT pRNFL analysis alone likely would overlook macular damage. Macular OCT imaging should be included in the imaging algorithm for the serial observation of patients with glaucoma. [ABSTRACT FROM AUTHOR]

Dorzolamide eye drops are widely prescribed to reduce intraocular pressure (IOP) in the treatment of ocular hypertension and glaucoma. However, in an eye drop formulation, dorzolamide is rapidly cleared from the preocular space, hence requiring multiple daily administrations. Here, we sought to increase the preocular retention of dorzolamide using nanostructured, mucoadhesive microparticles (MUCO_NM) as carriers for topical delivery to the eye. MUCO_NM were prepared by freeze-milling dorzolamide-loaded, electrospun nanofibers composed of poly(lactic-co-glycolic acid) and polyethylene glycol. The microparticles were embedded in a rapidly-dissolving tablet of polyvinyl alcohol. To assess in vivo efficacy, the MUCO_NM were administered topically to the eyes of rabbits, and IOP was measured and compared to that in eyes treated with Trusopt ® , a marketed eye drop of dorzolamide. The MUCO_NM showed a 35% greater maximum IOP decrease and a > 2-fold increase in the duration of the IOP decrease, compared to Trusopt ® . This enhanced efficacy was comparable to that obtained with a single administration of 4 drops of Trusopt ® or 2 administrations of Trusopt ® at a 4-h interval. Our findings suggest that this MUCO_NM preparation is a promising carrier for topical delivery of dorzolamide to the eye, with enhanced drug efficacy and the potential to reduce administration frequency. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether defects in cervical lymphatic drainage influence the intraocular pressure (IOP)-lowering effect of latanoprost in patients with primary open-angle glaucoma (POAG) who have undergone unilateral radical neck dissection (uRND). Methods: We enrolled (1) bilateral POAG patients who had started (bilateral) latanoprost (0.005%) monotherapy prior to their uRND and (2) treatment-naïve, bilateral glaucoma suspects (GSs) who had undergone the same surgery. We compared the eyes ipsilateral to the uRND with their fellow eyes in terms of the changes in IOP between the baseline (prior to the uRND) and the follow-up visits (1, 3, and 6 months after the uRND). Results: The study involved 22 eyes of 11 POAG patients and 14 eyes of 7 GSs. In the POAG patients, IOP had increased significantly after surgery in the eyes ipsilateral to the uRND (from 14.7±1.4mmHg to 17.1±2.2mmHg; P = 0.007). Interestingly, in the eyes contralateral to the uRND, IOP had not changed significantly after surgery (from 14.2±1.8mmHg to 14.4±2.0mmHg; P = 0.826). In GSs, the eyes ipsilateral to the uRND did not differ significantly from their fellow eyes in terms of post-operative IOP change (ipsilateral value: 0.3±0.5mmHg, fellow eyes: -0.1±0.7mmHg; P = 0.242). Conclusion: In the POAG patients, IOP had increased significantly in the eyes ipsilateral to the uRND. However, it had not changed significantly in the eyes contralateral to the surgery or in the eyes of the GSs. These findings suggest that, latanoprost works, at least in part, by enhancing outflow from the aqueous humor via the uveolymphatic pathway. [ABSTRACT FROM AUTHOR]

Purpose To investigate the frequency of focal abnormalities of the lamina cribrosa ( LC) in eyes with glaucomatous disc haemorrhage ( DH) using swept-source optical coherence tomography ( SS- OCT). Methods We analysed 72 glaucomatous eyes with DH (72 subjects) detected by masked grading of stereophotographs along with 63 glaucomatous eyes without DH (63 subjects) consecutively recruited from the cohort of DH Study from Seoul National University Hospital. All of the subjects underwent stereoscopic optic disc photography and in vivo SS- OCT LC imaging based on a customized optic disc scanning protocol (Topcon, Inc., Tokyo, Japan). Two masked graders evaluated each eye's serial en face images for focal LC defects. En face image/optic disc photograph overlay images were evaluated to determine the relationship between the respective focal LC defect and DH locations. Results Among the eyes with DH, the proportion with ≥1 LC defect was 80.6% (58 of 72 eyes), significantly higher than that for eyes without DH (39.7%, 25 of 63 eyes; p < 0.001). In the 58 eyes with DH and ≥1 LC defect, the location of the focal LC defect corresponded with that of the RNFL defect in 47 eyes (81.0%), and the location of the focal LC defect corresponded with the DH in 36 eyes (62.1%). Conclusions Focal LC defects are more frequently visible in eyes with glaucomatous DH than in eyes without DH. DH and LC defects, moreover, are often spatially correlated. These findings suggest that DH is associated with focal abnormalities of the LC. [ABSTRACT FROM AUTHOR]

Heart-related diseases account for a high proportion of deadly pathologies, so a large number of studies have been conducted to discover potential biomarkers for the early detection of heart disease. Circular RNAs (circRNAs) are known to be involved in various human diseases, and several circRNAs associated with heart disease have been reported recently. However, there is a lack of literature summarizing the potential of circRNAs as biomarkers of heart disease and suggesting future research prospects. In this review, the history of circRNA research and important studies on circRNAs are described. In addition, the biogenesis process of circRNAs and the applicability of circRNA as a biomarker of heart disease are introduced, and select studies that monitored circRNAs circulating in human blood as biomarkers of heart disease are summarized. The contents of this review may help the researchers interested in the detection and prevention of heart disease at an early stage. • The circRNAs are involved in various human diseases including heart diseases. • The history of circRNA research and important studies related to circRNA are described. • The circRNA as a biomarker related to heart disease is summarized. • The circRNAs measurement in the blood has sufficient reliability for diagnosing heart diseases. [ABSTRACT FROM AUTHOR]

Objective: To compare peripapillary and macular choroidal thickness (PCT and MCT) between open-angle glaucoma (OAG) and normal controls using swept-source optical coherence tomography (SS-OCT), and to evaluate global and localized relationships between choroidal thickness and various factors in OAG, also using SS-OCT. Methods: In this cross-sectional comparative study, 134 OAG patients and 73 normal controls were examined. PCT (global, 12 clock-hour sectors), MCT (global, six sectors) were measured by SS-OCT. The difference in choroidal thickness between the OAG patients and the normal controls was analyzed. The relationships between choroidal thickness and various factors including age, sex, spherical equivalent (SE), axial length (AXL), central corneal thickness (CCT), intraocular pressure (IOP), peripapillary retinal nerve fiber layer thickness (pRNFLT), visual field mean deviation (MD), ganglion cell-inner plexiform layer thickness (GCIPLT), and disc area were analyzed by univariate and multivariate linear regression. Global and regional analyses were performed in 12 segments of the peripapillary circle and in six sectors of the macula. Results: There were significant differences in global PCT and MCT between the OAG patients and the normal controls (115.22±41.17 vs. 138.89±44.70, P<0.001), (184.36±57.15 vs. 209.25±61.11, P = 0.004). The difference in global PCT remained, both after adjusting for age, AXL (117.08±3.45 vs. 135.47±4.70, P = 0.002) and also after adjusting for age, AXL, disc area (117.46±3.46 vs. 135.67±4.67, P = 0.002). But the difference in global MCT did not remain after adjusting for age, AXL, SE (188.18±4.46 vs. 202.25±6.08, P = 0.066). PCT showed significant differences between the groups in all of the 12 clock-hour sectors. These differences remained after adjusting for age, AXL and for age, AXL, disc area, with the exception of the 10 o’clock (o/c) sector. MCT in six sectors showed differences between the two groups, but they did not remain after adjusting for age, AXL, SE. In a multivariate regression analysis of the OAG patients, global PCT showed correlations with age (β = -1.18, P = 0.001), AXL (β = -14.01, P<0.001), and disc area (β = -16.67, P = 0.026). Global MCT, meanwhile, showed a significant correlation with age (β = -1.92, P<0.001), AXL. (β = -21.97, P<0.001). Choroidal thickness did not show any global or localized relationship with glaucoma severity in the OAG patients. Conclusions: The global and all 12 clock-hour PCT, with the exception of the 10 o/c sector, were thinner in OAG; however, they did not show any correlation with glaucoma severity. Possible roles of PCT in glaucoma pathogenesis should be investigated further. [ABSTRACT FROM AUTHOR]

Purpose To evaluate topographic correlations of the directions of β-zone peripapillary atrophy ( PPA) and optic disc torsion with retinal nerve fibre layer ( RNFL) defect in a Korean population. Methods Among 292 primary open-angle glaucoma ( POAG) patients from the 2012 KNHANES ( n = 7444, age ≥ 19 years), 93 eyes of 93 individuals with a single localized RNFL defect were enrolled. The angular locations of the point of maximum radial extent ( PMRE) of β-zone PPA and the optic disc torsion were measured on fundus photography. The angular location of the PMRE and the torsion degree ( TD) were noted when the absolute value of the former or the latter was ≥15 degrees from the reference line, a line drawn from the centre of the optic disc to the fovea. Results The overall POAG prevalence was estimated as 4.2% (95% confidence interval [ CI], 3.6-4.9). Of the POAG eyes with a single localized RNFL defect, 39.5% had superior or inferior PMRE of β-zone PPA; in 74.9% (p = 0.015) of those cases, the RNFL defect was located in the same hemifield as the angular location of the PMRE. Meanwhile, 40.4% of the POAG eyes with a single localized RNFL defect showed accompanying optic disc torsion. The correlation rate between the direction of the optic disc torsion and the RNFL defect location was 60.2% (p = 0.029). Conclusions In the Korean POAG patients examined, the directions of the PMRE of β-zone PPA and of the optic disc torsion showed significant associations with the RNFL defect location. [ABSTRACT FROM AUTHOR]

Topical drug administration to the eye is limited by low drug bioavailability due to its rapid clearance from the preocular surface. Thus, multiple daily administrations are often needed, but patient compliance is low, hence a high chance of unsatisfactory treatment of ocular diseases. To resolve this, we propose mucoadhesive microparticles with a nanostructured surface as potential carriers for delivery of brimonidine, an ocular drug for glaucoma treatment. For sustained drug delivery, the microparticles were composed mainly of a diffusion-wall material, poly(lactic-co-glycolic acid) and a mucoadhesive polymer, polyethylene glycol, was used as an additive. Due to their nanostructured surface, the microparticles with a mucoadhesive material exhibited a 13-fold increase in specific surface area and could thus adhere better to the mucous layer on the eye, as compared with the conventional spherical microparticles. When loaded with brimonidine, the mucoadhesive microparticles with a nanostructured surface increased both drug bioavailability and its activity period by a factor of more than 2 over Alphagan P, a marketed eye drop of brimonidine. [ABSTRACT FROM AUTHOR]

Purpose A MATLAB-based (The MathWorks, Inc, Natick, MA) computer program (the ganglion cell-inner plexiform layer [GCIPL] hemifield test) for automated detection of GCIPL thickness difference across the horizontal raphe was developed, and its glaucoma diagnostic performance was assessed. Design Cross-sectional study. Participants A total of 65 eyes of normal, healthy subjects along with 162 eyes of patients with glaucoma (79 preperimetric and 83 early perimetric). Methods Cirrus high-definition optical coherence tomography (HD-OCT) (Carl Zeiss Meditec, Dublin, CA) was used to scan all of the subjects' macular and optic discs. A positive (i.e., “outside normal limits”) GCIPL hemifield test result was declared if the following 3 conditions were all met: (1) The reference line (a horizontal line dividing the superior and inferior hemifields) is continuously detected for longer than one-half of the distance from the temporal inner elliptical annulus to the outer elliptical annulus; (2) the average GCIPL thickness difference within 10 pixels of the reference line, both above and below, is ≥5 μm; and (3) the average RGB color ranges of the 10 pixels above and below the reference line display blue in 1 hemifield and red/yellow/white in the other hemifield. Main Outcome Measures Comparison of diagnostic ability using the areas under the receiver operating characteristic curves (AUCs). Results A positive GCIPL hemifield test result was observed more frequently in the glaucomatous eyes (74/79 preperimetric, 78/83 early perimetric) than in the normal eyes (1/65). In the preperimetric group, the AUC of the GCIPL hemifield test (0.967; sensitivity 94.94%, specificity 98.46%) was greater than that of the minimum GCIPL thickness (0.933), the inferotemporal GCIPL thickness (0.907), and the average GCIPL thickness (0.899) ( P = 0.09, 0.06, and 0.03, respectively). In the early perimetric group, the AUC of the GCIPL hemifield test (0.962; sensitivity 93.98%, specificity 96.46%) was greater than that of the inferotemporal GCIPL thickness (0.938), the minimum GCIPL thickness (0.919), and the average GCIPL thickness (0.912) ( P = 0.38, 0.17, and 0.11, respectively). Conclusions For discrimination of early glaucomatous structural loss, most notably in preperimetric glaucoma cases, identification of the GCIPL thickness difference across the horizontal raphe was effective. [ABSTRACT FROM AUTHOR]

Objective: To investigate the 5-year incidence and progression rate of primary open-angle glaucoma (POAG) in a health-center-based Korean population. Methods: The study population comprised 5,021 subjects who participated in standardized health screening (including non-contact tonometry and fundus photography) at the Gangnam Healthcare Center during the period from January 2005 to December 2006 and again from January 2010 to December 2011. Among these subjects, 948 (18.9%) with findings suggestive of glaucoma were subjected to a comprehensive glaucoma evaluation, which included applanation tonometry and standard automated perimetry. Based on the results, the subjects were diagnosed as POAG suspect or definite POAG. Results: The 5-year incidences of POAG suspect and definite POAG were 0.84% (42 subjects) and 0.72% (36 subjects), respectively. The rate of progression from POAG suspect to definite POAG was 4.75% per year. In subjects with a baseline intraocular pressure (IOP) >21 mmHg, the incidence of POAG suspect or definite POAG was significantly higher than in those with a baseline IOP≤21 mmHg (32% vs. 1.05%; P<0.001). A multivariate analysis showed that the progression from POAG suspect to definite POAG was significantly associated with older age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03–1.10), higher baseline IOP (OR, 1.10; 95% CI, 1.01–1.24), higher body mass index (BMI) (OR, 1.15; 95% CI, 1.03–1.31), higher education level (OR, 1.57; 95% CI, 1.05–2.17), and higher hematocrit level (OR, 1.22; 95% CI, 1.08–1.43). Conclusions: In the health-center-based Korean population, the 5-year incidence of POAG was 0.72%, and the rate of progression from POAG suspect to definite POAG was 4.75% per year. This study identified old age, high baseline IOP, high BMI, high level of education, and high hematocrit level as significant risk factors for incident POAG. [ABSTRACT FROM AUTHOR]

Macular OCT angiography (OCTA) measurements have been reported to be useful for glaucoma diagnostics. However, research on highly myopic glaucoma is lacking, and the diagnostic value of macular OCTA measurements versus OCT parameters remains inconclusive. We aimed to evaluate the diagnostic ability of the macular microvasculature assessed with OCTA for highly myopic glaucoma and to compare it with that of macular thickness parameters, using deep learning (DL). A DL model was trained, validated and tested using 260 pairs of macular OCTA and OCT images from 260 eyes (203 eyes with highly myopic glaucoma, 57 eyes with healthy high myopia). The DL model achieved an AUC of 0.946 with the OCTA superficial capillary plexus (SCP) images, which was comparable to that with the OCT GCL+ (ganglion cell layer + inner plexiform layer; AUC, 0.982; P = 0.268) or OCT GCL++ (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer) images (AUC, 0.997; P = 0.101), and significantly superior to that with the OCTA deep capillary plexus images (AUC, 0.779; P = 0.028). The DL model with macular OCTA SCP images demonstrated excellent and comparable diagnostic ability to that with macular OCT images in highly myopic glaucoma, which suggests macular OCTA microvasculature could serve as a potential biomarker for glaucoma diagnosis in high myopia. [ABSTRACT FROM AUTHOR]

Various technical tools have been developed to probe the functions of microRNAs (miRNAs), yet their application has been limited by low efficacy and specificity. To overcome the limitations, we used transcription activator-like effector nucleases (TALENs) to knock out human miRNA genes. We designed and produced a library of 540 pairs of TALENs for 274 miRNA loci, focusing on potentially important miRNAs. The knockout procedure takes only 2-4 weeks and can be applied to any cell type. As a case study, we generated knockout cells for two related miRNAs, miR-141 and miR-200c, which belong to the highly conserved miR-200 family. Interestingly, miR-141 and miR-200c, despite their overall similarity, suppress largely nonoverlapping groups of targets, thus suggesting that functional miRNA-target interaction requires strict seed-pairing. Our study illustrates the potency of TALEN technology and provides useful resources for miRNA research. [ABSTRACT FROM AUTHOR]

Summary: Mammalian microRNAs (miRNAs) are highly stable in most cell types, and their decay mechanism remains largely unknown. Here we report that some miRNAs degrade rapidly upon the loss of cell adhesion. When cells are grown at low density or cells are detached by trypsinization or EGTA treatment, mature miR-141 is downregulated while miR-200c from a common primary transcript (pri-miR-200c∼141) remains unaffected. Blockade of transcription by Actinomycin D leads to rapid depletion of miR-141 with a half-life of <1 hr when cells are detached, indicating that the regulation occurs via RNA decay. A sequence motif (UGUCU) in the center of miR-141 is necessary for the regulation. We further find that many other miRNAs including miR-200a, miR-34a, miR-29b, miR-301a, and miR-21 are degraded upon cell splitting. Induced destruction of persistent regulatory molecules such as miRNAs may increase cellular plasticity and facilitate cellular remodeling in response to the changes in cell adhesion. [Copyright &y& Elsevier]

Small regulatory RNAs and their associated proteins are subject to diverse modifications that can impinge on their abundance and function. Some of the modifications are under the influence of cellular signaling, thus contributing to the dynamic regulation of RNA silencing. [Copyright &y& Elsevier]

Abstract: A new class of aryl amine derivatives, which contains phenylnaphthyldiamine core, has been synthesized and examined as a hole-transporting material (HTM) for organic light-emitting diodes (OLEDs). These phenylnaphthyldiamine derivatives possess high radical cation stabilities and high morphologic stabilities relative to their biphenyldiamine analogs. Theoretical experiments and OLED device fabrication were carried out to study their better hole-transporting properties. The electroluminescent devices with the phenylnaphthyldiamine derivatives HTM 2–4 as the hole-transporting layer were more efficient than that with the biphenyldiamine HTM 1. [Copyright &y& Elsevier]

Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol's effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation. [ABSTRACT FROM AUTHOR]

The majority of human microRNA (miRNA) loci are located within intronic regions and are transcribed by RNA polymerase II as part of their hosting transcription units. The primary transcripts are cleaved by Drosha to release ∼70 nt pre-miRNAs that are subsequently processed by Dicer to generate mature ∼22 nt miRNAs. It is generally believed that intronic miRNAs are released by Drosha from excised introns after the splicing reaction has occurred. However, our database searches and experiments indicate that intronic miRNAs can be processed from unspliced intronic regions before splicing catalysis. Intriguingly, cleavage of an intron by Drosha does not significantly affect the production of mature mRNA, suggesting that a continuous intron may not be required for splicing and that the exons may be tethered to each other. Hence, Drosha may cleave intronic miRNAs between the splicing commitment step and the excision step, thereby ensuring both miRNA biogenesis and protein synthesis from a single primary transcript. Our study provides a novel example of eukaryotic gene organization and RNA-processing control. [ABSTRACT FROM AUTHOR]

Abstract: A new class of tetraminobiphenyl derivatives, which contains a 3,3′,5,5′-tetraminobiphenyl core, has been synthesized and examined as a hole-transporting material for organic light-emitting diodes. We fabricated the organic light-emitting diode (OLED) cells with tetraminobiphenyl derivatives as hole-injecting layer, hole-transporting layer and hole-injecting and transporting layer for green device with tris(8-quinolinolato)aluminum (Alq3) doped with 1% of Coumarin 545T (C545T) as green emitting layer. Tetraminobiphenyls were found to be useful as a novel hole-transporting material. The electroluminescent device with the 3,3′,5,5′-tetrakis(p-tolyldiamino)biphenyl (TTAB) as a hole-transporting layer was more efficient than that with the analogous triarylamine, N,N′-di(naphthalene-1-yl)-N,N′-diphenyl benzidine (NPB). The external luminous efficiency of the device IV having TTAB as one hole-injecting and transporting layer can reach 14.55cd/A, which is higher than the standard device I (11.66cd/A) using two layers, a hole-injecting layer and a hole-transporting layer. [Copyright &y& Elsevier]

Abstract: Human vascular smooth muscle cells (HVSMCs) are resistant to Fas-mediated death under normal physiological conditions. However, HVSMC death by activation of the receptor pathway was reported in the atherosclerotic lesions. In this study, we investigated whether 7-ketocholesterol, one of the major cholesterol oxides in the lesions, altered resistance of HVSMC to Fas-mediated death pathway. Cross-linking of Fas receptor with agonistic anti-Fas antibody (CH11) in the presence of 7-ketocholesterol induced death in human aorta smooth muscle cells (HAoSMC) as detected by morphology, viability, and DNA fragmentation. The agonistic anti-Fas antibody, however, did not induce death in the presence of 7α-hydroxycholesterol or cholesterol. The HAoSMC death was significantly inhibited by an antagonistic Fas receptor (FasR) antibody and by expression of dominant negative Fas-associated death domain containing protein (DN-FADD) using adenoviruses. Activation of caspase-3 was observed in HAoSMC destined to death. HAoSMC death was significantly inhibited by pharmacological caspase inhibitor, z-VAD and z-DEVD, and baculovirus caspase inhibitor p35. 7-Ketocholesterol impaired mitochondrial transmembrane potential and ATP production. Overexpression of bcl-xL also significantly inhibited HAoSMC death. In dying HAoSMC, bax was translocated from the cytosol to mitochondria and cytochrome c was released from mitochondria into the cytosol. This is the first report demonstrating implication of the oxysterol in Fas-mediated death pathway. The present study proposes that 7-ketocholesterol would contribute to loss of HVSMC in the atherosclerotic lesions by altering resistance to receptor-mediated death pathway. [Copyright &y& Elsevier]

Cage-type molecules composed of phenyl walls and caps were synthesized as hosts for the binding of ammonium and alkali metal cations through cation-π interactions. The synthesis involved a key cyclization step, which was markedly dependent on the capping component. Binding studies by electrospray ionization mass spectrometry toward lithium, sodium, potassium, and ammonium cations showed that the cage-type molecules selectively form a 1:1 complex. A competitive binding study showed that cage 3c (R = Et, R′ = OMe) has a preference toward lithium cation while cage 4b (R = Me, R′ = OMe) has a similar preference toward both lithium and ammonium ion in the presence of others. This selectivity pattern was tentatively explained by the gate size of the cage-type compounds, not by their cavity size. [ABSTRACT FROM AUTHOR]

An experimental model of pressure-induced optic nerve damage promises to greatly expand understanding of the cellular events leading to retinal ganglion cell (RGC) death and of how they are influenced by intraocular pressure (IOP) and other risk factors associated with glaucoma. In this work, we propose a novel strategy employing photo-crosslinkable azidobenzoic acid-modified chitosan (Az-CH) for long-term, persistent elevation of IOP. For this purpose, a solution of Az-CH was injected into the anterior chamber of experimental rat eyes, which were subsequently irradiated with ultraviolet (UV) light to form an Az-CH gel that hindered aqueous outflow and effected prolonged IOP elevation thereby. The control eyes were treated as follows: (1) intracameral injection of Az-CH without UV irradiation, (2) intracameral injection of saline solution without UV irradiation or (3) no injection with UV irradiation. A significant IOP increase was observed in the experimental eyes, which was continuously higher for the whole testing period of 12 weeks after one-time treatment with Az-CH injection and UV irradiation. Also, a more significant loss of RGCs, one of the major features of glaucoma, was observed in experimental eyes than in the control eyes. Therefore, the strategy presented herein can be a novel experimental model to study the mechanism of RGC damage by elevated IOP over the course of a prolonged period. [Display omitted] • Novel glaucoma animal model with azidobenzoic acid-modified chitosan (Az-CH) • Intracamerally-injected Az-CH crosslinked by ultraviolet light irradiation • Persistent increase in intraocular pressure (IOP) for up to 12 weeks. • Significant loss of retinal ganglion cells (RGCs) [ABSTRACT FROM AUTHOR]

Introduction: Anterior segment optical coherence tomography (AS-OCT) is a non-contact, rapid, and high-resolution in vivo modality for imaging of the eyeball's anterior segment structures. Because progressive anterior segment deformation is a hallmark of certain eye diseases such as angle-closure glaucoma, identification of AS-OCT structural changes over time is fundamental to their diagnosis and monitoring. Detection of pathologic damage, however, relies on the ability to differentiate it from normal, age-related structural changes. Methods and analysis: This proposed large-scale, retrospective cross-sectional study will determine whether demographic characteristics including age can be predicted from deep learning analysis of AS-OCT images; it will also assess the importance of specific anterior segment areas of the eyeball to the prediction. We plan to extract, from SUPREME®, a clinical data warehouse (CDW) of Seoul National University Hospital (SNUH; Seoul, South Korea), a list of patients (at least 2,000) who underwent AS-OCT imaging between 2008 and 2020. AS-OCT images as well as demographic characteristics including age, gender, height, weight and body mass index (BMI) will be collected from electronic medical records (EMRs). The dataset of horizontal AS-OCT images will be split into training (80%), validation (10%), and test (10%) datasets, and a Vision Transformer (ViT) model will be built to predict demographics. Gradient-weighted Class Activation Mapping (Grad-CAM) will be used to visualize the regions of AS-OCT images that contributed to the model's decisions. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) will be applied to evaluate the model performance. Conclusion: This paper presents a study protocol for prediction of demographic characteristics from AS-OCT images of the eyeball using a deep learning model. The results of this study will aid clinicians in understanding and identifying age-related structural changes and other demographics-based structural differences. Trial registration: Registration ID with open science framework:10.17605/OSF.IO/FQ46X. [ABSTRACT FROM AUTHOR]

We previously showed that the matricellular protein CCN5 reverses established cardiac fibrosis (CF) through inducing apoptosis in myofibroblasts (MyoFBs) but not in cardiomyocytes or fibroblasts (FBs). In this study, we set out to elucidate the molecular mechanisms underlying CCN5-mediated selective apoptosis of MyoFBs. We first observed that the apoptotic protein p53 and the anti-apoptotic protein NFκB are simultaneously induced in MyoFBs. When the expression level of p53 was suppressed using a siRNA, CCN5 did not induce apoptosis in MyoFBs. By contrast, when NFκB signaling was inhibited using IKK VII, an IκB inhibitor, MyoFBs underwent apoptosis even in the absence of CCN5. SMAD7 is one of the downstream targets of CCN5 and it was previously shown to potentiate apoptosis in epithelial cells through inhibition of NFκB. In accordance with these reports, when the expression of SMAD7 was suppressed using a siRNA, NFκB signaling was enhanced, and CCN5 did not induce apoptosis. Lastly, we used a luciferase reporter construct to show that CCN5 positively regulated SMAD7 expression at the transcriptional level. Collectively, our data suggest that a delicate balance between the two mutually antagonistic proteins p53 and NFκB is maintained for MyoFBs to survive, and CCN5 tips the balance in favor of the apoptotic protein p53. This study provides insight into the anti-fibrotic activity of CCN5 during the regression of CF. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) contributes to multiple cellular mechanisms in the liver, muscle cells, adipose tissue, and brain, etc. In particular, the liver is an important organ in TH metabolism for the conversion of thyronine (T4) into triiodothyronine (T3) by the deiodinase enzyme. TH levels were significantly decreased and thyroid-stimulating hormone (TSH) levels were significantly increased in patients with liver failure compared with normal subjects. Among liver failure diseases, hepatic encephalopathy (HE) deserves more attention because liver damage and neuropathologies occur simultaneously. Although there is numerous evidence of TH dysregulation in the HE model, specific mechanisms and genetic features of the thyroid glands in the HE model are not fully understood. Here, we investigated the significantly different genes in the thyroid glands of a bile duct ligation (BDL) mouse model as the HE model, compared to the thyroid glands of the control mouse using RNA sequencing. We also confirmed the alteration in mRNA levels of thyroid gland function-related genes in the BDL mouse model. Furthermore, we evaluated the increased level of free T4 and TSH in the BDL mouse blood. Thus, we emphasize the potential roles of TH in liver metabolism and suggest that thyroid dysfunction-related genes in the HE model should be highlighted for finding the appropriate solution for an impaired thyroid system in HE. [ABSTRACT FROM AUTHOR]

In mobile robotics, obtaining stable image of a mounted camera is crucial for operating a mobile system to complete given tasks. This note presents the development of a high-speed image stabilizing device using linear shaft actuator, and a new image stabilization method inspired by human gaze stabilization process known as vestibulo-ocular reflex (VOR). In the proposed control, the reference is adaptively adjusted by the VOR adaptation control to reject residual vibration of a camera as the VOR gain converges to optimal state. Through experiments on a pneumatic vibrator, it will be shown that the proposed system is capable of stabilizing 10 Hz platform vibration, which shows potential applicability of the device to a high-speed mobile robot. [ABSTRACT FROM AUTHOR]

The matricellular protein CCN5 exerts anti-fibrotic activity in hearts partly by inducing reverse trans-differentiation of myofibroblasts (MyoFBs) to fibroblasts (FBs). CCN5 consists of three structural domains: an insulin-like growth factor binding protein (IGFBP), a von Willebrand factor type C (VWC), and a thrombospondin type 1 (TSP-1). In this study, we set out to elucidate the roles of these domains in the context of the reverse trans-differentiation of MyoFBs to FBs. First, human cardiac FBs were trans-differentiated to MyoFBs by treatment with TGF-β; this was then reversed by treatment with recombinant human CCN5 protein or various recombinant proteins comprising individual or paired CCN5 domains. Subcellular localization of these recombinant proteins was analyzed by immunocytochemistry, cellular fractionation, and western blotting. Anti-fibrotic activity was also evaluated by examining expression of MyoFB-specific markers, α-SMA and fibronectin. Our data show that CCN5 is taken up by FBs and MyoFBs mainly via clathrin-mediated endocytosis, which is essential for the function of CCN5 during the reverse trans-differentiation of MyoFBs. Furthermore, we showed that the TSP-1 domain is essential and sufficient for endocytosis and nuclear localization of CCN5. However, the TSP-1 domain alone is not sufficient for the anti-fibrotic function of CCN5; either the IGFBP or VWC domain is needed in addition to the TSP-1 domain. [ABSTRACT FROM AUTHOR]

Abstract: Eight alkamides 1–8 were isolated by bioassay-guided isolation of EtOH extracts of the fruits of Piper longum and Piper nigum (Piperaceae). Their structures were elucidated by spectroscopic analysis (1H, 13C NMR, and ESI-MS) as follows: guineensine (1), retrofracamide C (2), (2E,4Z,8E)-N-[9-(3,4-methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (3), pipernonaline (4), piperrolein B (5), piperchabamide D (6), pellitorin (7), and dehydropipernonaline (8). Their compounds 3–5, 7, and 8 inhibited potently the direct binding between sICAM-1 and LFA-1 of THP-1 cells in a dose-dependent manner, with IC50 values of 10.7, 8.8, 13.4, 13.5, and 6.0μg/mL, respectively. [Copyright &y& Elsevier]

• GLP-1 reduces neuroinflammation by regulating microglia function and polarization. • GLP-1 boosts the stabilization and recovery of neural connectivity in brain. • GLP-1 promotes spine maturation and enhances the improvement of spine function in neuron. Glucagon-like peptide-1 (GLP-1) is a hormone mainly secreted from enteroendocrine L cells. GLP-1 and its receptor are also expressed in the brain. GLP-1 signaling has pivotal roles in regulating neuroinflammation and memory function, but it is unclear how GLP-1 improves memory function by regulating neuroinflammation. Here, we demonstrated that GLP-1 enhances neural structure by inhibiting lipopolysaccharide (LPS)-induced inflammation in microglia with the effects of GLP-1 itself on neurons. Inflammatory secretions of BV-2 microglia by LPS aggravated mitochondrial function and cell survival, as well as neural structure in Neuro-2a neurons. In inflammatory condition, GLP-1 suppressed the secretion of tumor necrosis factor-alpha (TNF-α)-associated cytokines and chemokines in BV-2 microglia and ultimately enhanced neurite complexity (neurite length, number of neurites from soma, and secondary branches) in Neuro-2a neurons. We confirmed that GLP-1 improves neurite complexity, dendritic spine morphogenesis, and spine development in TNF-α-treated primary cortical neurons based on altered expression levels of the factors related to neurite growth and spine morphology. Given that our data that GLP-1 itself enhances neurite complexity and spine morphology in neurons, we suggest that GLP-1 has a therapeutic potential in central nervous system diseases. [ABSTRACT FROM AUTHOR]